CC BY 4.0 · Arq Neuropsiquiatr 2024; 82(06): s00431777806
DOI: 10.1055/s-0043-1777806
View and Review

Practices in the prescription of antiseizure medications: is it time to change?

Práticas na prescrição de medicamentos anticrise: está na hora de mudar?
1   Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Instituto Central, Divisão de Clínica Neurológica, São Paulo SP, Brazil.
2   Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Instituto de Psiquiatria, Programa de Neuropsiquiatria (PROJEPSI) São Paulo SP, Brazil.
,
3   Universidade Estadual de Campinas, Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas SP, Brazil.
4   Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Departamento de Neurologia, Campinas SP, Brazil.
,
3   Universidade Estadual de Campinas, Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas SP, Brazil.
4   Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Departamento de Neurologia, Campinas SP, Brazil.
,
3   Universidade Estadual de Campinas, Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas SP, Brazil.
4   Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Departamento de Neurologia, Campinas SP, Brazil.
,
3   Universidade Estadual de Campinas, Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas SP, Brazil.
4   Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Departamento de Neurologia, Campinas SP, Brazil.
,
3   Universidade Estadual de Campinas, Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas SP, Brazil.
4   Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Departamento de Neurologia, Campinas SP, Brazil.
› Author Affiliations

Abstract

The treatment of epilepsy has advanced over the past 30 years through the development of new antiseizure medications (ASMs). Unfortunately, not all of them have been approved yet in Brazil, and many are still underused. When comparing new ASMs to older ones, they are generally not more effective in treating epilepsy. However, they offer better tolerability, with fewer interactions and long-term side effects, especially for patients with comorbidities or those requiring polytherapy. Enzyme induction caused by older ASMs is associated with increased cholesterol levels, drug interactions with decreased effects of statins and other cardiovascular medications, anticoagulants, chemotherapy, immunosuppressors, anti-infective agents (including HIV treatment), antidepressants, and contraceptives. Additionally, they can reduce levels of vitamin D and sex hormones, as well as decrease bone density. The increasing concern about these effects during life, especially after prolonged exposure, has led most developed countries to change prescription patterns in favor of new ASMs, particularly levetiracetam and lamotrigine. Both are also considered the safest options for women of childbearing age. Regrettably, the prescription trends in Brazil have remained largely unchanged over time. This can be partially attributed to the slower approval process of ASM and the reluctance of general physicians and neurologists to embrace these new concepts. In this concise review, we highlight the various advantages linked to the new ASM, aiming to promote a shift in the prescription pattern for ASM. The selection of ASM should be customized according to individual characteristics, and practical suggestions for choosing ASMs are provided in this paper.

Resumo

O tratamento da epilepsia avançou nos últimos 30 anos com o desenvolvimento de novos medicamentos anticrise (MAC). Infelizmente, nem todos estão aprovados no Brasil e muitos ainda são subutilizados. Os novos MAC não são mais eficazes que os antigos, mas apresentam melhor tolerabilidade, menos interações e efeitos colaterais a longo prazo, especialmente para pacientes com comorbidades ou que necessitam de politerapia. A indução enzimática causada pelos MAC antigos está associada ao aumento dos níveis de colesterol, interações medicamentosas com redução do efeito das estatinas e outros medicamentos cardiovasculares, anticoagulantes, quimioterapia, imunossupressores, agentes anti-infecciosos (incluindo tratamento do HIV), antidepressivos e contraceptivos. Além disso, podem reduzir os níveis de vitamina D e hormônios sexuais, podendo afetar a massa óssea. A crescente preocupação sobre estes efeitos ao longo da vida, com a exposição prolongada, levou a maioria dos países desenvolvidos a modificar o padrão de prescrição com maior uso dos novos MAC, especialmente levetiracetam e lamotrigina. Ambos são considerados as opções mais seguras para mulheres em idade fértil. Infelizmente, as tendências de prescrição no Brasil permaneceram praticamente inalteradas ao longo do tempo. Isto pode ser parcialmente explicado pela lentidão no processo de aprovação dos MAC e à resistência dos médicos generalistas e neurologistas em adotar estes novos conceitos. Nesta revisão, destacamos as vantagens dos novos MAC e a necessidade da mudança no padrão de prescrição também no Brasil. A escolha do MAC deve ser feita de acordo com as características individuais dos pacientes e sugestões práticas são apresentadas.

Authors' Contributions

LFP, LSS, FC, CLY: conceptualization, data curation, formal analysis, investigation, methodology, project administration, supervision, validation, visualization, writing – original draft, writing – review & editing; RBJ, VB: data curation, methodology, project administration, validation, visualization, writing – original draft, writing – review & editing; LFP, LSS: these two authors contributed equally to the production of the manuscript.


Support

Fernando Cendes (CEPID-BRAINN; FAPESP 2013-0755903); Clarissa Lin Yasuda (CNPQ 315953/2021-7).




Publication History

Received: 22 October 2023

Accepted: 28 November 2023

Article published online:
26 March 2024

© 2024. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)

Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

Bibliographical Record
Lécio Figueira Pinto, Lucas Scárdua Silva, Rafael Batista João, Vinícius Boldrini, Fernando Cendes, Clarissa Lin Yasuda. Practices in the prescription of antiseizure medications: is it time to change?. Arq Neuropsiquiatr 2024; 82: s00431777806.
DOI: 10.1055/s-0043-1777806
 
  • References

  • 1 Chen B, Choi H, Hirsch LJ. et al. Cosmetic side effects of antiepileptic drugs in adults with epilepsy. Epilepsy Behav 2015; 42: 129-137
  • 2 Chen B, Choi H, Hirsch LJ. et al. Psychiatric and behavioral side effects of antiepileptic drugs in adults with epilepsy. Epilepsy Behav 2017; 76: 24-31
  • 3 Chen B, Choi H, Hirsch LJ, Legge A, Buchsbaum R, Detyniecki K. Cross-sensitivity of psychiatric and behavioral side effects with antiepileptic drug use. Seizure 2018; 62: 38-42
  • 4 Birbeck GL, French JA, Perucca E. et al; Quality Standards Subcommittee of the American Academy of Neurology, Ad Hoc Task Force of the Commission on Therapeutic Strategies of the International League Against Epilepsy. Evidence-based guideline: Antiepileptic drug selection for people with HIV/AIDS: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Ad Hoc Task Force of the Commission on Therapeutic Strategies of the International League Against Epilepsy. Neurology 2012; 78 (02) 139-145
  • 5 Glauser T, Ben-Menachem E, Bourgeois B. et al; ILAE Subcommission on AED Guidelines. Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia 2013; 54 (03) 551-563
  • 6 Perucca P, Gilliam FG. Adverse effects of antiepileptic drugs. Lancet Neurol 2012; 11 (09) 792-802
  • 7 Perucca E, Brodie MJ, Kwan P, Tomson T. 30 years of second-generation antiseizure medications: impact and future perspectives. Lancet Neurol 2020; 19 (06) 544-556
  • 8 Zaccara G, Perucca E. Interactions between antiepileptic drugs, and between antiepileptic drugs and other drugs. Epileptic Disord 2014; 16 (04) 409-431
  • 9 Marson AG, Kadir ZA, Hutton JL, Chadwick DW. The new antiepileptic drugs: a systematic review of their efficacy and tolerability. Epilepsia 1997; 38 (08) 859-880
  • 10 Chen Z, Brodie MJ, Kwan P. What has been the impact of new drug treatments on epilepsy?. Curr Opin Neurol 2020; 33 (02) 185-190
  • 11 Löscher W, Schmidt D. Modern antiepileptic drug development has failed to deliver: ways out of the current dilemma. Epilepsia 2011; 52 (04) 657-678
  • 12 Marson AG, Al-Kharusi AM, Alwaidh M. et al; SANAD Study group. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial. Lancet 2007; 369 (9566) 1000-1015
  • 13 Marson AG, Al-Kharusi AM, Alwaidh M. et al; SANAD Study group. The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial. Lancet 2007; 369 (9566) 1016-1026
  • 14 Mostacci B, Ranzato F, Giuliano L. et al. Alternatives to valproate in girls and women of childbearing potential with Idiopathic Generalized Epilepsies: state of the art and guidance for the clinician proposed by the Epilepsy and Gender Commission of the Italian League Against Epilepsy (LICE). Seizure 2021; 85: 26-38
  • 15 Cross JH, Tomson T. Newer versus older antiseizure medications: further forward?. Lancet 2021; 397 (10282): 1327-1329
  • 16 Lee SK. Old versus New: Why Do We Need New Antiepileptic Drugs?. J Epilepsy Res 2014; 4 (02) 39-44
  • 17 Brodie MJ, Mintzer S, Pack AM, Gidal BE, Vecht CJ, Schmidt D. Enzyme induction with antiepileptic drugs: cause for concern?. Epilepsia 2013; 54 (01) 11-27
  • 18 Mintzer S, Trinka E, Kraemer G, Chervoneva I, Werhahn KJ. Impact of carbamazepine, lamotrigine, and levetiracetam on vascular risk markers and lipid-lowering agents in the elderly. Epilepsia 2018; 59 (10) 1899-1907
  • 19 Brämswig S, Sudhop T, Luers C, von Bergmann K, Berthold HK. Lipoprotein(a) concentration increases during treatment with carbamazepine. Epilepsia 2003; 44 (03) 457-460
  • 20 Bullman J, Nicholls A, Van Landingham K. et al. Effects of lamotrigine and phenytoin on the pharmacokinetics of atorvastatin in healthy volunteers. Epilepsia 2011; 52 (07) 1351-1358
  • 21 Josephson CB, Wiebe S, Delgado-Garcia G. et al. Association of Enzyme-Inducing Antiseizure Drug Use With Long-term Cardiovascular Disease. JAMA Neurol 2021; 78 (11) 1367-1374
  • 22 Mäkinen J, Rainesalo S, Raitanen J, Saarinen J, Sandell S, Peltola J. Discontinuation of carbamazepine due to concerns of long-term consequences of enzyme induction. Epilepsia Open 2018; 3 (03) 340-347
  • 23 Elger CE, Rademacher M, Brandt C. et al. Changes in hormone and lipid levels in male patients with focal seizures when switched from carbamazepine to lacosamide as adjunctive treatment to levetiracetam: A small phase IIIb, prospective, multicenter, open-label trial. Epilepsy Behav 2016; 62: 1-5
  • 24 Asconapé JJ. The selection of antiepileptic drugs for the treatment of epilepsy in children and adults. Neurol Clin 2010; 28 (04) 843-852
  • 25 Shepard PW, St Louis EK. Seizure treatment in transplant patients. Curr Treat Options Neurol 2012; 14 (04) 332-347
  • 26 Tomson T, Battino D, Bromley R. et al. Management of epilepsy in pregnancy: a report from the International League Against Epilepsy Task Force on Women and Pregnancy. Epileptic Disord 2019; 21 (06) 497-517
  • 27 Cohen JM, Alvestad S, Cesta CE. et al. Comparative Safety of Antiseizure Medication Monotherapy for Major Malformations. Ann Neurol 2023; 93 (03) 551-562
  • 28 Alsfouk BAA, Brodie MJ, Walters M, Kwan P, Chen Z. Tolerability of Antiseizure Medications in Individuals With Newly Diagnosed Epilepsy. JAMA Neurol 2020; 77 (05) 574-581
  • 29 Assis T, Bacellar A, CÔrtes L, Santana S, Costa G, Nascimento O. Trends in prescribing patterns of antiepileptic drugs among older adult inpatients in a Brazilian tertiary center. Arq Neuropsiquiatr 2021; 79 (01) 22-29
  • 30 Bertoldi AD, Helfer AP, Camargo AL, Tavares NU, Kanavos P. Is the Brazilian pharmaceutical policy ensuring population access to essential medicines?. Global Health 2012; 8: 6
  • 31 Powell G, Logan J, Kiri V, Borghs S. Trends in antiepileptic drug treatment and effectiveness in clinical practice in England from 2003 to 2016: a retrospective cohort study using electronic medical records. BMJ Open 2019; 9 (12) e032551
  • 32 Borghs S, Thieffry S, Noack-Rink M. et al. Health care cost associated with the use of enzyme-inducing and non-enzyme-active antiepileptic drugs in the UK: a long-term retrospective matched cohort study. BMC Neurol 2017; 17 (01) 59
  • 33 Willems LM, Hamer HM, Knake S, Rosenow F, Reese JP, Strzelczyk A. General Trends in Prices and Prescription Patterns of Anticonvulsants in Germany between 2000 and 2017: Analysis of National and Cohort-Based Data. Appl Health Econ Health Policy 2019; 17 (05) 707-722
  • 34 Chen Z, Brodie MJ, Liew D, Kwan P. Treatment Outcomes in Patients With Newly Diagnosed Epilepsy Treated With Established and New Antiepileptic Drugs: A 30-Year Longitudinal Cohort Study. JAMA Neurol 2018; 75 (03) 279-286
  • 35 Khanna S, Pillai KK, Vohora D. Insights into liaison between antiepileptic drugs and bone. Drug Discov Today 2009; 14 (7-8): 428-435
  • 36 Vecht CJ, Wagner GL, Wilms EB. Interactions between antiepileptic and chemotherapeutic drugs. Lancet Neurol 2003; 2 (07) 404-409
  • 37 St Louis EK. Truly “rational” polytherapy: maximizing efficacy and minimizing drug interactions, drug load, and adverse effects. Curr Neuropharmacol 2009; 7 (02) 96-105
  • 38 Verrotti A, Tambucci R, Di Francesco L. et al. The role of polytherapy in the management of epilepsy: suggestions for rational antiepileptic drug selection. Expert Rev Neurother 2020; 20 (02) 167-173
  • 39 Mattson RH, Cramer JA, McCutchen CB. Barbiturate-related connective tissue disorders. Arch Intern Med 1989; 149 (04) 911-914
  • 40 Margolis JM, Chu BC, Wang ZJ, Copher R, Cavazos JE. Effectiveness of antiepileptic drug combination therapy for partial-onset seizures based on mechanisms of action. JAMA Neurol 2014; 71 (08) 985-993
  • 41 Mei PA, Montenegro MA, Guerreiro MM, Guerreiro CA. Pharmacovigilance in epileptic patients using antiepileptic drugs. Arq Neuropsiquiatr 2006; 64 ( 2A): 198-201
  • 42 National Guideline A. NICE Evidence Reviews Collection. Effectiveness of antiseizure therapies in the treatment of idiopathic generalised epilepsies, including juvenile myoclonic epilepsy: Epilepsies in children,. young people and adults: Evidence review J. London: National Institute for Health and Care Excellence (NICE) Copyright © NICE 2022., 2022
  • 43 Cerulli Irelli E, Morano A, Cocchi E. et al. Doing without valproate in women of childbearing potential with idiopathic generalized epilepsy: Implications on seizure outcome. Epilepsia 2020; 61 (01) 107-114
  • 44 Asadi-Pooya AA, Rostaminejad M, Zeraatpisheh Z, Mirzaei Damabi N. Cosmetic adverse effects of antiseizure medications; A systematic review. Seizure 2021; 91: 9-21
  • 45 Witt JA, Helmstaedter C. Monitoring the cognitive effects of antiepileptic pharmacotherapy–approaching the individual patient. Epilepsy Behav 2013; 26 (03) 450-456
  • 46 Zaccara G, Lattanzi S. Comorbidity between epilepsy and cardiac arrhythmias: Implication for treatment. Epilepsy Behav 2019; 97: 304-312
  • 47 Garoufi A, Vartzelis G, Tsentidis C. et al. Weight gain in children on oxcarbazepine monotherapy. Epilepsy Res 2016; 122: 110-113 DOI: 10.1016/j.eplepsyres.2016.03.004.
  • 48 Löscher W, Klein P. The Pharmacology and Clinical Efficacy of Antiseizure Medications: From Bromide Salts to Cenobamate and Beyond. CNS Drugs 2021; 35 (09) 935-963
  • 49 Bialer M, White HS. Key factors in the discovery and development of new antiepileptic drugs. Nat Rev Drug Discov 2010; 9 (01) 68-82
  • 50 Rosenberg EC, Chamberland S, Bazelot M. et al. Cannabidiol modulates excitatory-inhibitory ratio to counter hippocampal hyperactivity. Neuron 2023; 111 (08) 1282-1300.e8
  • 51 Patsalos PN, Szaflarski JP, Gidal B, VanLandingham K, Critchley D, Morrison G. Clinical implications of trials investigating drug-drug interactions between cannabidiol and enzyme inducers or inhibitors or common antiseizure drugs. Epilepsia 2020; 61 (09) 1854-1868
  • 52 Agência Nacional de Vigilância Sanitária (ANVISA). Consultas. 2023
  • 53 Food and Drug Administration (FDA). FDA-Approved Drugs. 2023
  • 54 Jin K, Obara T, Hirano K. et al. Prescription trends in anti-seizure medications for adult patients with epilepsy in Japan: A retrospective cohort study using the database of health insurance claims between 2015 and 2019. Epilepsy Behav 2022; 134: 108841
  • 55 Yu L, Zhu W, Zhu X, Lu Y, Yu Z, Dai H. Anti-seizure Medication Prescription in Adult Outpatients With Epilepsy in China, 2013-2018. Front Neurol 2021; 12: 649589
  • 56 Terman SW, Youngerman BE, Choi H, Burke JF. Antiseizure medication treatment pathways for US Medicare beneficiaries with newly treated epilepsy. Epilepsia 2022; 63 (06) 1571-1579
  • 57 Terman SW, Lin CC, Kerr WT, DeLott LB, Callaghan BC, Burke JF. Changes in the Use of Brand Name and Generic Medications and Total Prescription Cost Among Medicare Beneficiaries With Epilepsy. Neurology 2022; 99 (08) e751-e761
  • 58 Hochbaum M, Kienitz R, Rosenow F. et al. Trends in antiseizure medication prescription patterns among all adults, women, and older adults with epilepsy: A German longitudinal analysis from 2008 to 2020. Epilepsy Behav 2022; 130: 108666